Diabetic Neuropathy sometimes can be reversed by vitamin D

See also VitaminDWiki

• Diabetic Retinopathy associated with low Vitamin D - many studies
• Search for Neuropathy in VitaminDWiki 356 items as of Sept 2017
• Peripheral neuropathy is 2.6 times more likely if low vitamin D – June 2016
• Peripheral Neuropathy in type II Diabetes reduced a bit by 50,000 IU weekly of vitamin D – RCT Feb 2015
• Diabetic neuropathy reduced by injection of 600,000 IU of vitamin D – Feb 2016
• Diabetic Nephropathy – active vitamin D helps – Dec 2014
• Overview Diabetes and vitamin D
• Kidney disease helped by active or high dose Vitamin D - Feb 2014
• 50 percent of Chronic Kidney Disease treatments in Germany include vitamin D – Dec 2012
• ALL autoimmune peripheral neuropathy patients had low vitamin D levels – Oct 2014
• Diabetic neuropathy least likely if have 30-40 ng of vitamin D – Oct 2015
• All items in Diabetes and Vitamin D 551 items
• Can Vitamin D TREAT Diabetes - many articles TREAT, not just prevent
• ALL autoimmune peripheral neuropathy patients had low vitamin D levels – Oct 2014
• Diabetic Neuropathy sometimes can be reversed by vitamin D collection of many PN studies
• Diabetic neuropathy least likely if have 30-40 ng of vitamin D – Oct 2015
• INTERVENTION Clinical Trials for Diabetes and Vitamin D 197 trials as of Sept 2017

Items in both categories Kidney and Vitamin D Receptor:

Items in both categories Diabetes and Intervention

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See also web on Peripheral Neuropathy

• Statin Drugs and PN Green Med Info] 6 abstracts as of Feb 2013
• The Causes of Peripheral Neuropathy Will Astound and Surprise You... Easy Immune Health: B12, Vitamin D, Vitamin E, Thiamine,
• Is Nerve Damage The Rule, Not the Exception With Cholesterol Meds? Mercola Jan 2012
  If You Take Statins for Two Years or More, Nerve Damage Appears to be the Rule

Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes. June 2011, full text online

• retinopathy was 2x more likely with Vitamin D deficiency

Does Vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes? Jan 2012

• diabetic peripheral neuropathy 3.5X more likely if vitamin D deficiency

Forum discussion on Diabetic Neuropathy 2008

Clinical Trial: Vitamin D Supplementation in Diabetic Nephropathy

• Looking to treat Diabetic Nephropathy 40,000 IU vitamin D monthly

Can vitamin D reverse nerve damage from diabetes? Review of the next item by Vitamin D Council

• The prevalence of diabetic neuropathy is approximately 20%
• Diabetic neuropathy is implicated in 50–75% of all diabetic amputations.

Reversal of the Symptoms of Diabetic Neuropathy through Correction of Vitamin D Deficiency in a Type 1 Diabetic Patient – Dec 2012

Hindawi Publishing Corporation Case Reports in Endocrinology Volume 2012, Article ID 165056, 3 pages doi:10.1155/2012/165056
David S. H. Bell
Southside Endocrinology, University of Alabama Medical School, Suite 130, 3928 Montclair Road, Birmingham, AL 35213, USA Correspondence should be addressed to David S. H. Bell, dshbell at yahoo.com Received 12 November 2012; Accepted 2 December 2012 Academic Editors: T. Cheetham and R. Swaminathan

Vitamin D deficiency has been associated with both type 1 and type 2 diabetes as well as both the microvascular and macrovascular complications of diabetes. Vitamin D deficiency has been shown to be more common in diabetic patients who have symptoms of distal symmetrical polyneuropathy. In addition, vitamin D deficiency has been associated with a lower pain threshold which increases when vitamin D deficiency is corrected. Herein, I describe a type 1 diabetic patient with neuropathic symptoms so severe that he could not work and for which he needed narcotics for pain management and whose symptoms improved dramatically with correction of the vitamin D deficiency. To my knowledge, this is the first report of an improvement in severe symptoms of diabetic neuropathy with correction of vitamin D deficiency in a single patient.

1. Introduction

Vitamin D deficiency has in addition to bone disease been implicated as a factor or cofactor in the etiology of type 2 diabetes, type 1 diabetes and other autoimmune diseases, heart disease, and cancers [1]. In addition, vitamin D deficiency is often diagnosed in those with established diabetes and vitamin D replacement may prevent or delay the onset of diabetic complications [2]. In addition pain thresholds of multiple etiologies have been reported to be lowered with vitamin D deficiency and elevated when the vitamin D deficiency is corrected [3].

When distal symmetrical neuropathy is diagnosed in a diabetic patient, causes other than diabetes itself are seldom found. However, it is recommended that a paraproteinemia and vitamin B12 deficiency are eliminated with a plasma protein electrophoresis and vitamin B12 level. Vitamin B12 deficiency is common in patients who utilize metformin for treatment of their type 2 diabetes, and there is also a higher prevalence ofpernicious anemia with type 1 diabetes.

2. Clinical Presentation

A 38-year-old type 1 (C-peptide < 0.01ng/mL) diabetic patient had had diabetes for 27 years and neuropathic symptoms (tingling, burning, shooting pains, and paresthesias) in both hands and feet for 10 years with an escalation of the severity ofsymptoms occurring during the previous four years.

Initially, he had partial relief of his symptoms with tri-cyclics, gabapentin, and pregabalin. However, his symptoms became so severe that he had to stop working, and for pain control he required narcotic analgesia (oxycodone) which only marginally ameliorated his symptoms. Objective findings were typical of a small fiber neuropathy with preservation of reflexes and vibration sense with hyperesthesia to painful stimuli to the level of the ankles bilaterally.
Both vitamin B12 deficiency and a paraproteinemia were ruled out as a cause of his neuropathic symptoms, and his HbA1c was 7.0%. A 25-OH-vitamin D level was preformed because the patient was obese (6'2" 245 lbs) (BMI 31.5), and obesityaswellastype1diabetesisoftenassociatedwith low vitamin D levels [1]. Based on his 25-OH-vitamin D level which was 16.5 ng/dL he was started on 50,000 units of vitamin D2 weekly, and within two weeks his symptoms began to decrease. Within four weeks his symptoms had improved to a level at which he was able to discontinue his oxycodone and at that time his symptoms were controlled with clonazepam 2 mg daily and sinequan 150 mg hs. A repeat 25-hydroxy-vitamin D level after one month of therapy was 48 ng/dL.

3. Discussion

If a proven vitamin deficiency exists then correction of the deficiency maybe beneficial and not cause harm. However, if a vitamin level is in the normal range additional vitamin supplementation is of no value and can be harmful [1]. In this case, correction of the vitamin D deficiency was undertaken only to prevent the development of the protean manifestations of vitamin D deficiency and not to treat the symptoms of diabetic neuropathy [1]. However, to my surprise repletion of vitamin D resulted in a very significant improvement in his neuropathic symptoms. This to my knowledge is the first report of the symptoms of severe and disabling diabetic neuropathy being improved by correction of the vitamin D deficiency in an individual patient.

Neuropathy in some shape or form occurs in 60-70% of diabetic patients with 50% of these patients experiencing varying degrees of neuropathic pain which invariably results in a decreased quality of life [4]. The question which remains unanswered in this case is whether the correction of vitamin D deficiency simply resulted in a nonspecific elevation of the pain threshold as has been described by Plotnkoff et al. or was due to a specific pathological improvement in the affected nerves or was it due to a combination of elevating the pain threshold and an amelioration of nerve damage [3].

Animal studies have shown that vitamin D deficiency is associated with low levels of neurotrophins (especially nerve growth factor) and defective neuronal calcium homeostasis. In addition vitamin D through its receptor modulates neuronal differentiation as well as neuronal growth and function [5]. In rats, the production of nerve growth factor which is required for the development and survival of both sympathetic and sensory neurons decreases in the presence of vitamin D deficiency. In fact, in vitamin D deficient diabetic animals correction of vitamin D deficiency resulted in an improvement in nerve growth factor production [6]. Decrease in neurotrophins and defective calcium homeosta-sis leaves the nerve vulnerable to toxins including hyper-glycemia. As a result, a deficiency of vitamin D impairs noci-ceptor function, worsens nerve damage, and lowers the pain threshold [6].

In humans in the National Health and Nutrition Examination Survey, vitamin D deficiency (defined as a level less than 30 ng/mL) in adults diabetes was associated with, after statistical correction for the HbA1c level, with the symptoms (numbness, pain, loss of feeling, and tingling in the hands and/or feet) of diabetic neuropathy [7].

In another study vitamin D levels were not only inversely proportional to a neuropathy symptoms score but also showed a statistically significant (OR 3.47 95% CI 1.0411.56 P = 0.04) association with slower nerve conduction velocities after correction for duration of diabetes and levels of HbA1c, LDL, and urinary albumin [8].

Prospectively, a nonrandomized study of 51 type 1 diabetic subjects with painful diabetic neuropathy showed a 50% decrease in pain scores with vitamin D repletion [9]. However, the neuropathic pain level in this group was much less than the severe pain level described by this individual patient. In addition, in humans topical vitamin D application to the areas affected by neuropathy has been reported to relieve neuropathic symptoms [10].

Therefore, this case study where severe neuropathic symptoms were corrected by restoring vitamin D levels into normal range validates the previous studies of less severe neuropathic symptoms [9, 10]. From the patient's and the clinician's viewpoint whether the improvement in symptoms is due to improvement in nerve damage or simply due to a nonspecific vitamin D induced elevation of the pain threshold is of little consequence and only of academic interest.

I would therefore propose that in all diabetic patients presenting with symptomatic or nonsymptomatic neuropathy a 25-OH vitamin D level is obtained and that if the 25-OH-vitamin D level is less than 30 ng/mL, therapy with vitamin D2 or D3 is initiated to elevate the 25-OH vitamin D level to a level of above 30 ng/mL.

The correction of vitamin D deficiency cannot be harmful and has the potential to alleviate neuropathic symptoms and lower the need for medications especially narcotics with their often severe side effects. In addition with correction of vitamin D deficiency, there is the potential of arresting and perhaps reversing the progression of neuronal destruction.

References

[1] D. S. H. Bell, "Protean manifestations of vitamin D deficiency, part 2: deficiency and its association with autoimmune disease, cancer, infection, asthma, dermopathies, insulin resistance, and type 2 diabetes," Southern Medical Journal, vol. 104, no. 5, pp. 335-339, 2011.
[2] A. G. Pittas, J. Lau, F. B. Hu, and B. Dawson-Hughes, "The role ofvitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis," Journal ofClinical Endocrinology and Metabolism, vol. 92, no. 6, pp. 2017-2029, 2007.
[3] G. A. Plotnikoff and J. M. Quigley, "Prevalence of severe hyp-ovitaminosis D in patients with persistent, nonspecific mus-culoskeletal pain," Mayo Clinic Proceedings, vol. 78, no. 12, pp. 1463-1470, 2003.
[4] C. E. Argoff,B.E.Cole,D.A.Fishbain, andG.A.Irving, "Diabetic peripheral neuropathic pain: clinical and quality-of-life issues," Mayo Clinic Proceedings, vol. 81, no. 4, supplement, pp.S3-S11,2006.
[5] S. Riaz, M. Malcangio, M. Miller, and D. R. Tomlinson, "A vitamin D3 derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats," Diabetologia, vol. 42, no. 11, pp. 1308-1313, 1999.
[6] R. Mascarenhas and S. Mobarhan, "Hypovitaminosis D-induced pain," Nutrition Reviews, vol. 62, no. 9, pp. 354-359, 2004.
[7] L.H.Soderstrom,S.P.Johnson,V.A.Diaz,andA.G.Mainous, "Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001-2004 NHANES," Diabetic Medicine, vol. 29, no. 1, pp. 50-55, 2012. in VitaminDWiki
[8] D. Shehab, K. Al-Jarallah, O. A. Mojiminiyi, H. Al Mohamedy, and N. A. Abdella, "Does Vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes?" Diabetic Medicine, vol. 29, no. 1, pp. 43-49, 2012.
[9] P. Lee and R. Chen, "Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain," Archives ofInternal Medicine, vol. 168, no. 7, pp. 771-772, 2008.
[10] P. Valensi, C. Le Devehat, J. L. Richard et al., "A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy: a preliminary report," Journal of Diabetes and its Complications, vol. 19, no. 5, pp. 247-253, 2005.

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Exercise + Vitamin D (400 IU + 1 gram Calcium Carbonate) helpes Diabetic Neuropathy in many ways - May 2017

The Comparison between Effects of 12 weeks Combined Training and Vitamin D Supplement on Improvement of Sensory-motor Neuropathy in type 2 Diabetic Women.
Adv Biomed Res. 2017 May 2;6:55. doi: 10.4103/2277-9175.205528. eCollection 2017.
Nadi M1, Marandi SM1, Esfarjani F1, Saleki M2, Mohammadi M3.

BACKGROUND:
Peripheral neuropathy is a common complaint of diabetes. This study aimed to determine the effects of 12 weeks combined training with Vitamin D supplement on improvement of sensory-motor neuropathy in women with diabetic neuropathy.

MATERIALS AND METHODS:
This clinical trial study conducted on 90 patients were selected and randomly divided into two groups. Finally, 81 adult females with diabetes type II (20-55 years old) were interred in this study. The control group had no training, but received Vitamin D. The experimental group received Vitamin D and 12 weeks training program (3 days a week, 60 min/session) including aerobic exercises, strength, and flexibility. Aerobic exercise intensity was set at 60-70% maximum heart rate and resistance training intensity was determined by 10 R.M. Michigan neuropathy questionnaire, reflex hammer and tuning fork 128 Hz used to screening tense of neuropathy (Michigan Neuropathy Screening Instrument) that were used for pretest and posttest.

RESULTS:
Following 3 months combined training and supplementation with Vitamin D, had observed a significant reduction in

• numbness (P = 0.001),
• pain (0.002), tingling (P = 0.001), and
• weakness (P = 0.002) in the lower limb and also
• increases in sense of touch intervention (P = 0.005),
• detects the position of the fingers (P = 0.001) and
• vibration perception (P = 0.001) in tissues.
• Knee reflexes (P = 0.77) and ankles reflexes (P = 0.47) did not significantly change after interventions.

CONCLUSION: It seems that taking part in combined training and supplementation with Vitamin D can improve the symptoms of sensory-motor neuropathy.

PMID: 28553628 PMCID: PMC5434674 DOI: 10.4103/2277-9175.205528
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The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy - July 2016

abstract and free PDF online

Vitamin D for the treatment of painful diabetic neuropathy - Feb 2016

600,000 IU Vitamin D injection   abstract and free PDF online